4 research outputs found
In vivo nanoscale analysis of the dynamic synergistic interaction of Bacillus thuringiensis Cry11Aa and Cyt1Aa toxins in Aedes aegypti.
- Author
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2021
- Field of study
The insecticidal Cry11Aa and Cyt1Aa proteins are produced by Bacillus thuringiensis as crystal inclusions. They work synergistically inducing high toxicity against mosquito larvae. It was proposed that these crystal inclusions are rapidly solubilized and activated in the gut lumen, followed by pore formation in midgut cells killing the larvae. In addition, Cyt1Aa functions as a Cry11Aa binding receptor, inducing Cry11Aa oligomerization and membrane insertion. Here, we used fluorescent labeled crystals, protoxins or activated toxins for in vivo localization at nano-scale resolution. We show that after larvae were fed solubilized proteins, these proteins were not accumulated inside the gut and larvae were not killed. In contrast, if larvae were fed soluble non-toxic mutant proteins, these proteins were found inside the gut bound to gut-microvilli. Only feeding with crystal inclusions resulted in high larval mortality, suggesting that they have a role for an optimal intoxication process. At the macroscopic level, Cry11Aa completely degraded the gastric caeca structure and, in the presence of Cyt1Aa, this effect was observed at lower toxin-concentrations and at shorter periods. The labeled Cry11Aa crystal protein, after midgut processing, binds to the gastric caeca and posterior midgut regions, and also to anterior and medium regions where it is internalized in ordered "net like" structures, leading finally to cell break down. During synergism both Cry11Aa and Cyt1Aa toxins showed a dynamic layered array at the surface of apical microvilli, where Cry11Aa is localized in the lower layer closer to the cell cytoplasm, and Cyt1Aa is layered over Cry11Aa. This array depends on the pore formation activity of Cry11Aa, since the non-toxic mutant Cry11Aa-E97A, which is unable to oligomerize, inverted this array. Internalization of Cry11Aa was also observed during synergism. These data indicate that the mechanism of action of Cry11Aa is more complex than previously anticipated, and may involve additional steps besides pore-formation activity
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- Author
- Abad Vanessa
- Abate Getahun
- Abbas Anum
- Ackerman Jamie
- Ackerman Ronald
- Ackermann Jeremy
- Adams Atoya
- Adams Mark S.
- Adams Michael R.
- Adelglass Jeffrey
- Afework Sarah
- Ahmad Nina
- Akamine Christine
- Ake Julie A.
- Al-Ibrahim Mohamed S.
- Albert Gary
- Alcaide Maria L.
- Alderson Nathan
- Aleman Lily
- Alemán José O.
- Allaw Mohammed
- Alva E. Javier Pretell
- Alvarado Hilario
- Amador Carmen
- Andersen James
- Anderson Corey G.
- Anderson Evan J.
- Anderson Victoria R.
- Andes David R.
- Andrasik Michele P.
- Andree Stephanie
- Andrews Jeb
- Andriesen Jessica G.
- Andriulis Victoria
- Ansel Jessica L.
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- Antwi Mohammed
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- Takizala Zudi-Mwak
- Takuva Simbarashe G.
- Talaat Kawsar R.
- Tan Chen S.
- Tapia Milagritos
- Tarakjian Denis
- Tashima Karen
- Tatelbaum David
- Taylor Barbara S.
- Taylor Brandie
- Tedder-Edwards Sharita
- Teherani Meghan
- Theodore Deborah A.
- Thessing Jeffrey
- Thomas Meagan
- Thomas-Seaton LaTeshia
- Thompson Amy
- Thompson Karl M.
- Thompson-Seim Teri
- Thomsen Isaac
- Tieu Hong V.
- Toma Ramy J.
- Tomaszewski Christian
- Tomatsu Lee
- Tomlinson Ryan
- Tong Tina
- Tong Xiaomi
- Torres Juan P.
- Torres Julian A.
- Tovar Dalia
- Tran Carolyn
- Treanor John J.
- Tukuru Sade
- Turley Christine B.
- Turner Mark A.
- Tyson Stefanie
- Ulrich Robert J.
- Usdan Lisa S.
- Utz Gregory C.
- Vachris Timothy P.
- Valenti Bruno
- Valika Insiya
- Van Der Leden Mimi
- Van Dromme Ilse
- Van Ever Wesley
- Van Roey Griet
- Varughese Tilly
- Vega Jocelyn Zuleica Olmos
- Vega Norma
- Vegas Diana
- Vertucci Michele
- Viar Veronica
- Viens Nicholas A.
- Villegas Marysol
- Vingerhoets Johan
- Vogler Mary
- Vowell Mandy
- Vrbicky Keith W.
- Wahlin Tami
- Wakefield Paul H.
- Wald Anna
- Walker James
- Walker Shannon
- Walsh Edward E.
- Walsh Mary C.
- Walsh Stephen R.
- Walsh Stephen R.
- Walter Emmanuel B.
- Walters Ayanna
- Wang Tina
- Warden Ashley
- Waters Michael
- Watkins Breanz
- Webb Angella
- Webster Hala
- Weidler Jessica L.
- Weiss Thomas
- Wells Margaret
- Wendell Lewis III
- Wendrow Andrea
- Werne Melody
- West Whitney
- Whatley Jordan L.
- Whitaker Jennifer A.
- White Jewel J.
- White Julie
- White Toni
- Wijewardane Priyantha N.
- Wilkin Timothy
- Wilkinson Bethanie
- William S. Davis Jr
- Williams Barton G.
- Williams Hayes
- Williams Samantha
- Wilson Christine
- Wilson Clint
- Wilson Greg
- Wilson Natasha
- Winbigler Jennifer
- Winkle Peter J.
- Winokur Patricia L.
- Witbeck John
- Wohl David
- Woo Wayne
- Woodside Leana
- Wortman Glenn
- Wu Yi H.
- Wylie Paul E.
- Yang Fan
- Yang Kinara S.
- Yoon Anelgine C.
- York Jill
- Young Cheryl
- Yu Chenchen
- Yusin Joseph
- Zapata Luz
- Zash Rebecca
- Zegarra Eneyda Giuvanela Llerena
- Zemanek Arthur L.
- Zenlea Kate
- Zepeda Karla
- Zervos Marcus J.
- Zhai Nan
- Zhang Kevin
- Zhou James
- Zimmer Andrea
- Zingman Barry S.
- Zorrilla Carmen D.
- Áñez Germán
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/10/2023
- Field of study
Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health
Risk of COVID-19 after natural infection or vaccinationResearch in context
- Author
- A. Lina Rosengren
- Abram Burgher
- Adam B. Brosz
- Adam Rosen
- Adam Schwartz
- Adriana Sordo Duran
- Adrienna Marquez
- Adrienne E. Shapiro
- Aeiress Duhart
- Afsoon Roberts
- Albert Liu
- Alejandro Hoberman
- Alejandro Quintín Barrat Hernández
- Alex Greninger
- Alexander Clark
- Alfredo Gilberto Guerreros Benavides
- Alice McGarry
- Alicia Arrazcaeta
- Alisha Lutat
- Alison Bondell
- Alison Pellecchia
- Allie Oplinger
- Allison Green
- Allison O'Brien
- Alpa Patel
- Alyssa-Kay Peay
- Amanda Horn
- Amanda Lilienthal
- Amanda Occhino
- Amanda Philyaw
- Amaran Moodley
- Amber Grant
- Amber Stanford
- Amesika Nyaku
- Amie Shannon
- Amina Z. Haggag
- Amit Paliwal
- Amy Caldwell
- Amy Chamberlain
- Amy Dye
- Amy Falk
- Amy Kelley
- Amy Medina
- Amy Potts
- Amy Salzl
- Amy Sherman
- Amy Starr
- Amy Thompson
- Andrea Berry
- Andrea Clement
- Andrea Wendrow
- Andrea Zimmer
- Andres Bran
- Andres Camacho-Gonzalez
- Andrew Lauria
- Andrew McConnell
- Andrew McWilliams
- Anelgine C. Yoon
- Angela Lee
- Angela R. Branche
- Angelica Kottkamp
- Angella Webb
- Ann M. Milliken
- Ann R. Falsey
- Anna S. Lok
- Anna Wald
- Anne Marit de Groot
- Anne-Marie Rick
- Annette R. Bennett
- Annie Ciambruschini
- Annie Luetkemeyer
- Anthony Kim
- Anum Abbas
- Anyela Lara
- April Pixler
- Ariana C. Stanton
- Arthur L. Zemanek
- Asha Inniss
- Ashley Kennedy
- Ashley Perez
- Ashley Warden
- Asif Noor
- Atoya Adams
- Aurelio Cruz-Valdez
- Austin Chan
- Austin Swanson
- Ayanna Walters
- Ayoade Avworo
- Bailey Jordan
- Barbara Corral
- Barbara Rizzardi
- Barbara Rizzardi
- Barbara S. Taylor
- Barry S. Zingman
- Barton G. Williams
- Beatriz Grinsztejn
- Becky Martinez
- Ben Ladner
- Benjamin Eckhardt
- Benjamin J. Luft
- Bernard Grunstra
- Beth Safirstein
- Bethanie Wilkinson
- Beverly E. Sha
- Beverly Ewing
- Bindu Balani
- Blanca Gomez
- Bo Shopsin
- Boerries Brandenburg
- Brandie Taylor
- Brandon J. Essink
- Brandy Ball
- Breanz Watkins
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- Brett Gray
- Brett Leav
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- Brit Sovic
- Brittany Feijoo
- Brittany Stewart
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- Bruce G. Rankin
- Bruce McClenathan
- Bruno Valenti
- Bryan Gordon
- C. Mary Healy
- Caitlin J. Guiney
- Caitlin Moran
- Candace Smith
- Candice Montros
- Carina A. Rodriguez
- Carl Fichtenbaum
- Carl P. Griffin
- Carlos A. Fierro
- Carlos del Rio
- Carlos Lopez
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- Carmel B. Dyer
- Carmen A. Paez
- Carmen Amador
- Carmen D. Zorrilla
- Carmen Medina
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- Carol Kauffman
- Carol L. Mitchell
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- Carolyn Tran
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- Carrie Sopher
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- Catherine Mary Healy
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- Chelsea Miles
- Chelsie Nutsch
- Chelsie Nutsch
- Chen S. Tan
- Chenchen Yu
- Cheryl Nuss
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- Chinar Desai
- Christian Tomaszewski
- Christina A. Rostad
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- Riemke Brakema
- Ripley R. Hollister
- Robert Brownlee
- Robert J. Buynak
- Robert J. Ulrich
- Robert Jeanfreau
- Robert L. Atmar
- Robert M. Grossberg
- Robert Riesenberg
- Robert S. Call
- Robert Samuels
- Robert Schmidt
- Robert Striker
- Robert W. Coombs
- Robert W. Frenck Jr.
- Roberto A. Viau Colindres
- Roberto C. Arduino
- Robin Hilder
- Robin Mason
- Robyn Hartvickson
- Rodney E. Sturgeon
- Roger J. Bedimo
- Rola G. Rucker
- Ronald Ackerman
- Ronald Lubelchek
- Roni Gray
- Rosa MacBryde
- Rosa Negron
- Rosamond Hong
- Rosario Sanchez
- Rozeli Shelly
- Rusty Greene
- Ruth Paiano
- Ruth S. Pinilla
- Ryan C. Maves
- Ryan Israelsen
- Ryan Little
- Ryan P. Starr
- Ryan Tomlinson
- S. Hasan Naqvi
- Saadia Khizer
- Sabina Raja
- Sade Tukuru
- Sally Eppenbach
- Samantha Williams
- Samira Shairi
- Sandra Erickson
- Sandra Janeth Ortega Domínguez
- Sandra Kelman
- Sandra Shelton
- Sarah Afework
- Sarah Dzigiel
- Sarah E. Rutstein
- Sarah Galloway
- Sarah Gordon
- Sarah M. Ingalsbe-Geno
- Sarah Omodele
- Satoshi Kamidani
- Sauda Muhammad
- Scott Borgetti
- Scott Kahney
- Scott N. Syndergaard
- Sebastian Garcia Escallon
- Secia Díaz-Miralrio
- Sergio E. Recuenco
- Sha-Wanda Richmond
- Shamika Huskey
- Shana Harshell
- Shanda Gower
- Shane G. Christensen
- Shannen Seversen
- Shannon Rodman
- Shannon Walker
- Sharine Phan
- Sharita Tedder-Edwards
- Sharon A. Riddler
- Sharon E. Frey
- Sharon Kohrs
- Sharon Nachman
- Sharzhaad Molina Guizar
- Shashi Kapadia
- Shauna H. Gunaratne
- Sheetal Kandiah
- Shelby Olds
- Shelby Pickle
- Sherif Naguib
- Sherrie Baker
- Sherry Lamberth
- Sheryl L. Henderson
- Shireen H. Jaffer
- Shishir K. Khetan
- Shivanjali Shankaran
- Shobha Swaminathan
- Sigridh Muñoz-Gómez
- Siham Mahgoub
- Sikhongi Phungwayo
- Silvano Omar Martínez Pérez
- Simbarashe G. Takuva
- Simmy Pinto
- Sinikka L. Green
- Sonal Munsiff
- Sonia Guerrero
- Sonja Neumeister
- Spyros A. Kalams
- Srilatha Edupuganti
- Stacy Ford
- Stacy Slechta
- Stanford Plavin
- Stefanie Mott
- Stefanie Tyson
- Stephan C. Sharp
- Stephan Hong
- Stephanie Andree
- Stephanie Rolsma
- Stephanie Skipper
- Stephanie Sterling
- Stephen A. Spector
- Stephen Daniels
- Stephen Morris
- Stephen R. Walsh
- Stephen R. Walsh
- Steve Clemons
- Steven E. Carsons
- Steven Palmer
- Steven Shinn
- Steven Shoptaw
- Steven Sperber
- Stuart H. Cohen
- Surisday Mederos
- Susan Jeanfreau
- Susan Kline
- Susan L. Koletar
- Susan Parker
- Susanne Doblecki-Lewis
- Suzanna Studdard
- Suzanne Fiorillo
- Suzanne Gharib
- Suzanne Swan
- Sybil G. Hosek
- Szheckera Fearon
- Tamara Richards
- Tambra Dora
- Tameika Scott
- Tami Wahlin
- Tammi L. Shlotzhauer
- Tana Bourgeois
- Tanya Hutchins
- Taryn Petty
- Tatiana Beresnev
- Tavane Harrison
- Taylor Nelson
- Teletha Gipson
- Teresa A. Batteiger
- Teresa Becker
- Teresa Deese
- Teresa S. Sligh
- Teri Thompson-Seim
- Terri Moye
- Terry D. Klein
- Terry L. Poling
- Terry Piedra
- Theresa Hegmann
- Thomas B. Campbell
- Thomas C. Klein
- Thomas C.S. Martin
- Thomas Mellman
- Thomas Patterson
- Thomas Weiss
- Tiffany Esinhart
- Tiffany Nemecek
- Tiffany Schwasinger-Schmidt
- Tilly Varughese
- Timothy J. Hatlen
- Timothy P. Vachris
- Timothy Shope
- Timothy W. Schacker
- Timothy Wilkin
- Tina Tong
- Tina Wang
- Toby Briskin
- Todd Simmons
- Tom Fiel
- Toni Robinson
- Toni White
- Tracy Okonya
- Tracy R. Klein
- Trina L. Reynolds
- Troy Holdeman
- Tyler D. Bold
- Uriel R. Felsen
- Valentine M. Ebuh
- Valeria D. Cantos
- Valerie K. Arnold
- Vanessa Abad
- Vanessa Raabe
- Veronica G. Fragoso
- Veronica Garcia-Fragoso
- Veronica Procasky
- Veronica Viar
- Vicki E. Miller
- Vickie Leathers
- Victoria Andriulis
- Victoria Engler
- Victoria Mosteller
- Victoria R. Anderson
- Vida Veronica Ruiz Herrera
- Vincent Huynh
- Vincent Mirkil
- Vivek Rajasekhar
- Viviana Gonzalez
- Vladimir Berthaud
- Walter Patton
- Wanda Ramon
- Waseem Chughtai
- Wayne L. Harper
- Wayne Woo
- Wendell Lewis
- Wendell Lewis III
- Wendy A. Keitel
- Wesley Campbell
- Wesley Van Ever
- Westly Keating
- Whitney West
- Will Hernandez
- William B. Davis
- William B. Smith
- William H. Jones
- William Jennings
- William Kirby
- William P. Silver
- William R. Hartman
- William S. Davis Jr.
- William Schnitz
- William Seger
- Winniberg Stephany Alvarez León
- Winston Cavert
- Xiaomi Tong
- Yaa D. Oppong
- Yi H. Wu
- Ying Huang
- Yogesh K. Paliwal
- Youyi Fong
- Yunda Huang
- Yunda Huang
- Yvonne Davis
- Zachary Bittner
- Zainab Rizvi
- Zindy Yazmín Zárate Hinojosa
- Zudi-Mwak Takizala
- Publication venue
- Elsevier
- Publication date
- 01/10/2023
- Field of study
Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- Author
- Abad Jorge
- Abad Sebastien
- Abassi Radhiya
- Abdelhadi Nour Mekki
- Abdellaoui Abdelrafie
- Abdelmalek Abdelkrim
- Abdoul Hendy
- Abel Laurent
- Abel Laurent
- Abel Laurent
- Abel Laurent
- Abergel Helene
- Abeud Fariza
- Abgrall Sophie
- Abisror Noemie
- Abolhassani Hassan
- Abou Tayoun Ahmad
- Accordino Giulia
- Achille Cristian
- Adechian Marylise
- Aderdour Nordine
- Admane Hakeem Farid
- Adnet Frederic
- Afritt Sara
- Agostini Helene
- Agra Juan José Cáceres
- Aguilar Claire
- Aguilera-Albesa Sergio
- Aguiló-Cucurull Aina
- Agut Sophie
- Aiello Tommaso Francesco
- Aiuti Alessandro
- Ajeenthiravasan Gokula
- Akcan Özge Metin
- Al-Muhsen Saleh
- Al-Muhsen Saleh Zaid
- Al-Mulla Fahd
- Alauzy Virginie
- Alavi Darazam Ilad
- Alavoine Loubna
- Alba Camille
- Albisures Jonathan Antonio Roblero
- Alby-Laurent Fanny
- Aldave Juan C.
- Algera Anne Geke
- Aliberti Anna
- Alkan Gulsum
- AlKhater Suzan A.
- Allard Lucie
- Allardet-Servent Jerome
- Allende Luis M.
- Alonso-Arias Rebeca
- Alosaimi Mohammed Faraj
- Alshahrani Mohammed S.
- Alsina Laia
- Alsohime Fahad M.
- Alvarez Josep Trenado
- Alyanakian Marie-Alexandra
- Alyanakian Marie-Alexandra
- Amam Sabrina
- Amara Yasmina Ould
- Amat Karine
- Amoura Zahir
- Amrouche Lucile
- Amsterdam UMC Covid-19 Biobank [missing]
- Anderson Mark S.
- Andreakos Evangelos
- Andrejak Claire
- Andronikof Marc
- Anglicheau Dany
- Angoulvant François
- Anguel Nadia
- Annane Djillali
- Antolí Arnau
- Aounzou Mohammed
- Aparicio Caroline
- Appelman Brent
- Aratus Gladys
- Arias Andrés A.
- Arias Andrés Augusto
- Arlet Jean-Benoit
- Arquero Miguel Fernandez
- Arranz María Jesús
- Arrestier Romain
- Arzoine Jeremy
- Asano Takaki
- Aslangul Elisabeth
- Assefi Mona
- Aubart Mélodie
- Aubry Adeline
- Audiffred Laetitia
- Audureau Etienne
- Auger Christelle Nathalie
- Auguet Teresa
- Auregan Jean-Charles
- Avramenko Iryna
- Awotar Celine
- Aytekin Gokhan
- Aytekin Gökhan
- Aytekin Selma Erol
- Azan Delphine
- Azemar Laurene
- Azot Axelle
- Azzouguen Billal
- Bachelet Delphine
- Badsi Aïda
- Baghdadi Jamila El
- Bahram Seiamak
- Bajolle Fanny
- Bakouboula Prissile
- Balcerowiak Coline
- Baldanti Fausto
- Balde Fanta
- Baldivia Elodie
- Baldolli Aurélie
- Ballester Maite
- Bangamingo Eliane-Flore
- Baptiste Amandine
- Baran-Marszak Fanny
- Barau Caroline
- Barget Nathalie
- Baris-Feldman Hagit
- Baronnet Flore
- Barrou Benoit
- Barthelemy Romain
- Bartoli Marie
- Barzaghi Federica
- Basmaci Romain
- Basso Sabrina
- Bastard Paul
- Baudel Jean-Luc
- Baudry Camille
- Baudry Elodie
- Bauters Fre
- Bax Diane
- Bayhan Gulsum Iclal
- Beaugerie Laurent
- Behilill Sylvie
- Behillil Sylvie
- Belamri Adel
- Belaube Nicolas
- Belilita Rhida
- Bellani Giacomo
- Bellassen Pierre
- Belmokhtar Rawan
- Belot Alexandre
- Belot Alexandre
- Beltran Isabel
- Beluze Marine
- Benainous Ruben
- Benallaoua Mourad
- Benamouzig Robert
- Benbara Amélie
- Benhida Jaouad
- Benkerrou Dehbia
- Benkhelouf Anis
- Benlagha Jihene
- Benmostafa Chahinez
- Benothmane Skander
- Bentifraouine Miassa
- Berard Laurence
- Beretta Ilaria
- Bergman Peter
- Berkell Matilda
- Bernier Quentin
- Bertholon Frédérique
- Berti Enora
- Bertier Astrid
- Berton Laure
- Bessis Simon
- Bettini Laura Rachele
- Beudel Martijn
- Beurton Alexandra
- Bezrodnik Liliana
- Bhavsar Krishna
- Bianco Celine
- Bianquis Clara
- Bidar Frank
- Biggs Catherine M.
- Bilbao Agurtzane
- Biondi Andrea
- Bizien Lucy
- Blanchard-Rohner Geraldine
- Blanche Philippe
- Blanco Ignacio
- Blandinières Adeline
- Blayau Clarisse
- Bleibtreu Alexandre
- Bleibtreu Alexandre
- Blin Emmanuelle
- Bloch-Queyrat Coralie
- Bloomfield Marketa
- Blázquez-Gamero Daniel
- Bogaard Harm Jan
- Bogunovic Dusan
- Boissier Marie-Christophe
- Boisson Bertrand
- Boisson-Dupuis Stephanie
- Boland Anne
- Bolivar-Prados Mireia
- Bollens Diane
- Bolze Alexandre
- Bolzoni Marion
- Bomers Marije
- Bompard Rudy pierre
- Bondarenko Anastasiia
- Bondarenko Anastasiia
- Bondesan Simone
- Bonnet Nicolas
- Bonnouvrier Justine
- Bonta Peter
- Borghesi Alessandro
- Borie Raphael
- Borrero Blanca Amador
- Borrero Blanca Amador
- Bos Lieuwe
- Bosteels Cedric
- Botdhlo-Nevers Elisabeth
- Botelho-Nevers Elisabeth
- Botha Shirmonecrystal
- Botta Michela
- Bouadma Lila
- Boucenna Wissam
- Bouchama Fatiha
- Bouchaud Olivier
- Bouchez Sabelline
- Bouchghoul Hanane
- Boudjebla Taoueslylia
- Boudjema Noel
- Bouffard Catherine
- Bougle Adrien
- Bouguerra Meriem
- Bouiller Kévin
- Boulanger Cécile
- Bouras Leila
- Bourcier Agnes
- Bourgeon Marilou
- Bourrier Anne
- Bouscambert Maude
- Bouscarat Fabrice
- Bousfiha Ahmed A.
- Bousfiha Ahmed A.
- Bousquet Aurore
- Boutolleau David
- Bouvattier Claire
- Bouvry Diane
- Bouziri Nesrine
- Bouzrara Ons
- Boyarchuk Oksana
- Bozdemir Şefika Elmas
- Bravais Juliette
- Bribier Sarah
- Briones M. Luisa
- Brodin Petter
- Brouwer Matthijs C.
- Brugier Delphine
- Bruneau Léa
- Brunel Melanie
- Brunner Marie-Eve
- Bruno Raffaele
- Bryceson Yenan
- Bryceson Yenan T.
- Bueno Maria Rita P.
- Bugiani Marianna
- Bui Eida
- Buis David T. P.
- Buisson Anne
- Bukhari Huda
- Bukreyeva Iryna
- Bulle Esther
- Burdet Charles
- Bureau Côme
- Bureau Serge
- Bustamante Carlos D.
- Bustamante Jacinta
- Bustos Ingrid G.
- Butte Manish J.
- Cabrera-Marante Oscar
- Cadranel Jacques
- Cailhol Johann
- Calin Ruxandra
- Canavaggio Pauline
- Cancella Marta
- Cantin Delphine
- Cao Albert
- Capra Ruggero
- Carapito Raphael
- Carbillon Lionel
- Carcel Sheila
- Carelli Valerio
- Carlier Nicolas
- Carrabba Maria
- Carrera Paola
- Casanova Jean-Laurent
- Casanova Jean-Laurent
- Casari Giorgio
- Casasnovas Carlos
- Caseris Marion
- Cassaniti Irene
- Cassard Clementine
- Castelle Martin
- Castelli Francesco
- Castor Guylaine
- Castro Mateus V.
- Catherinot Emilie
- Cauchy Marion
- Cazzaniga Marina
- Celik Jale Bengi
- Cervantes-Gonzalez Minerva
- Ceschi Alessandro
- Cha Olivier
- Chachoua Abla
- Chahine Abir
- Chaigne Benjamin
- Chair Anissa
- Chakravorty Samya
- Chaldebas Matthieu
- Challal Salima
- Chalumeau Martin
- Chalumeau Nathalie Costedoat
- Champion Karine
- Charbit Bruno
- Chariot Patrick
- Charpentier Charlotte
- Chas Julie
- Chauveau Simon
- Chauvin Anthony
- Chauvin Clement
- Chavarot Nathalie
- Chaïbi Khalil
- Chebbout Kamélia
- Cheng Matthew P.
- Cherai Mustapha
- Cherubini Ilaria
- Chevalier Amelie
- Chiarabini Thibault
- Chinet Thierry
- Chirouze Catherine
- Chirouze Catherine
- Chocron Richard
- Choinier Pascaline
- Chommeloux Juliette
- Choquet Christophe
- Choupeaux Laure
- Chousterman Benjamin
- Christelle Kouakam
- Christodoulou John
- Ciocan Dragosmarius
- Citerio Giuseppe
- Clarke Ada
- Clavere Gaëlle
- Clavier Florian
- Clavé Père
- Clement Karine
- Clerc Sebastien
- Cloherty Osoul Chouchane Alex
- Clotet Bonaventura
- Cobat Aurélie
- Codina Anna
- Coelho Alexandra
- Cohen Adrien
- Cohen Fleur
- Cohen Yves
- Cohen Yves
- Coilly Audrey
- Colboc Hester
- Colin Pauline
- Collet Magalie
- Colobran Roger
- Comarmond Chloé
- Comarmond Cloé
- Combacon Emeline
- Combe Caroline Lascoux
- Combes Alain
- Combes Alain
- Comoli Patrizia
- Comparon Celine
- Condino-Neto Antonio
- Constantin Jean-Michel
- Constantinescu Stefan N.
- Contro Ernesto
- Cooper Megan A.
- Cordel Hugues
- Cordier Anne-Gael
- Corsico Angelo G.
- Costantini Adrien
- Couffignal Camille
- Couffignal Camille
- Couffin-Cadiergues Sandrine
- Couffin-Cadiergues Sandrine
- Coupeau Doriane
- CoV-Contact Cohort [missing]
- COVID Clinicians [missing]
- COVID Human Genetic Effort [missing]
- COVID-STORM Clinicians [missing]
- COVIDeF Study Group [missing]
- Covill Laura E.
- Coşkuner Taner
- Creange Alain
- Cuadros Esmeralda Nuñez
- Cvetkovski Aleksandar
- Cyrus Cyril
- Da Silveira Charlène
- Dalgard Clifton L.
- Dalmau David
- Danielson Jeffrey J.
- Danion François
- Darley David Ross
- Das Vincent
- Dauby Nicolas
- Dauger Stéphane
- De Bouille Jeanne Goupil
- de Brabander Justin
- de Bree Godelieve
- de Bruin Sanne
- De Castro Nathalie
- De Chambrun Marc Pineton
- de Chambrun Marc Pineton
- de Diego Rebeca Pérez
- De Farcy Pauline Mary
- de Jong Menno D.
- De Munter Paul
- de Pontual Loic
- de Rotte Maurits C. F. J.
- De Rycke Yann
- de Vera Martín Castillo
- de Vries Heder
- Debray Marie-Pierre
- Dechanet Aline
- Declercq Jozefien
- Deconinck Lauren
- Dehban Amin
- Del Pozo Lucie
- del Prado Maria Yolanda Ruiz
- Delannoy Quentin
- Delay Mathieu
- Deleris Robin
- Deleuze Jean-François
- Delforge Juliette
- Delmonte Ottavia M.
- Delphine Laëtitia
- Delplancq Geoffroy
- Demar Magalie
- Demare Noemie
- Demeret Sophie
- Demerville Lauren
- Demirkol Yasemin Kendir
- Demoule Alexandre
- Demoule Alexandre
- Deniau Aurore
- Deplanque Dominique
- Deplanque Dominique
- Depret François
- Derolez Sophie
- Derradji Ouda
- Derridj Nawal
- Desai Murkesh
- Descamps Diane
- Descamps Diane
- Descamps Vincent
- Deschamps Lydia
- Desconclois Celine
- Desguerre Isabelle
- Desille-Dugast Mireille
- Desmarets Maxime
- Desnos Cyrielle
- Desongins Karine
- Desvallée Mathilde
- Devouge Eglantine Ferrand
- Dhote Robin
- Di Sabatino Antonio
- Diallo Alpha
- Diallo Benjamin
- Didier Morgane
- Diehl Jean-Luc
- Diemer Myriam
- Diez Stephane
- Dijkstra Mirjam
- Diouf Alphonsine
- Djadi-Prat Juliette
- Djebara Siham
- Djebra Naoual
- Djietcheu Minette
- Djillali Hadjer
- Djossou Félix
- Djouadi Nouara
- Dobbelaere Stephanie
- Dobbs Kerry
- Domínguez-Garrido Elena
- Dongelmans Dave A.
- Donneger Severine
- Dorival Céline
- Dos Santos Catarina
- Dournon Nathalie
- Dres Martin
- Droctove Laura
- Drogrey Marie
- Drolet Beth A.
- Dropy Margot
- Drouet Elodie
- Dubos François
- Dubosq Valérie
- Dubost Clément
- Dubreucq Evelyne
- Dubus Estelle
- Duchemann Boris
- Duchenoy Thibault
- Dudoignon Emmanuel
- Dufau Romain
- Dujardin Romein W. G.
- Dumas Florence
- Duran Clara
- Durand Anne Bourgarit
- Duron Emmanuelle
- Durrbach Antoine
- Duval Xavier
- Duval Xavier
- Duvivier Claudine
- D’Angio’ Mariella
- d’Ortenzio Eric
- Ebstein Nathan
- Ecobichon Jean-Luc
- Ekwall Olov
- El Zein Loubna
- Elabbadi Alexandre
- Elbers Paul
- Elharrar Brigitte
- Elie Caroline
- Elnagdy Marwa H.
- Eloy Philippine
- Elrufaai Marwa Bachir
- Emiroglu Melike
- Endo Akifumi
- Enouf Vincent
- Enouf Vincent
- Erdeniz Emine Hafize
- Ernotte Gabriel
- Esling Anne
- Esperou Hélène
- Espinosa-Padilla Sara
- Esposito-Farese Marina
- Espérou Hélène
- Etienne Manuel
- Etienne Martin
- Euvrard Romain
- Eyer Xavier
- Fabio Giovanna
- Faivre Laurence
- Falck Antonin
- Fartoukh Muriel
- Fartoukh Muriel sarah
- Faure Morgane
- Fayali Takoua
- Feldman Hagit Baris
- Feldman Hagit Baris
- Fellay Jacques
- Fermaut Marion
- Ferrer Ricard
- Ferreres Jose
- Fiorentino Alessio
- Fiorentino Arianna
- Fleuren Lucas
- Fliss Souha
- Flores Carlos
- Florkin Benoit
- Foti Giuseppe
- Fouchard Julie
- Fournier Benjamin
- Fournier Marie-Céline
- Franco Jose Luis
- Franco José Luis
- Francois Bruno
- Francois Hélène
- French COVID Cohort Study Group [missing]
- Freynet Olivia
- Frezouls Wahiba
- Frigout Yvann
- Froidure Antoine
- Fromont Isaure
- Fuentes Axelle
- Fumadó Victoria
- Fung Kitty S. C.
- Furet Thomas
- Fusco Francesca
- Gagneux-Brunon Amandine
- Gagro Alenka
- Galand Joris
- Garnier Marc
- Garçon Pierre
- Gatineau Audrey Giraud
- Gaubert Agnes
- Gaudry Stéphane
- Gaugain Samuel
- Gault Nathalie
- Gaussem Pascale
- Gauthier Damien
- Gautier Maxime
- Gaymard Alexandre
- Gayretli Zeynep
- Geijtenbeek Suzanne Geerlings Theo
- Georgin-Lavialle Sophie
- Geromin Daniela
- Gervais Adrian
- Ghalayini Mohamed
- Ghaleh Bijan
- Ghezal Myriam
- Ghosn Jade
- Gibelin Aude
- Gigante Tristan
- Gil-Herrera Juana
- Gilardin Laurent
- Gilg Morgane
- Gimeno Linda
- Girard Benoit
- Girbes Armand
- Girona-Alarcón Mònica
- Gissot Valérie
- Goas Carole L. E.
- Godínez Karen Alejandra Cifuentes
- Goffard Jean-Christophe
- Gomes Doryan
- Gomes-Pires Elisabete
- Gonzales Nacho
- Gonzalez-Granado Luis I.
- González-Montelongo Rafaela
- Goorhuis Bram
- Gorochov Guy
- Gouge Anne
- Gouja Amel
- Goulet Helene
- Goupil Sylvain
- Gras Julien
- Greffe Segolene
- Gregersen Peter K.
- Grimaldi Lamiae
- Grobusch Martin P.
- Guedeney Paul
- Guedj Jérémie
- Guerder Antoine
- Guidet Bertrand
- Guillo Matthias
- Gulczynski Mariechristelle
- Gumucio Victor Daniel
- Gunst Jan
- Gut Marta
- Gysembergh-Houal Anne
- Gérardin Patrick
- Gülhan Belgin
- Hadjadj Jérôme
- Hadjam Tassadit
- Haerynck Filomeen
- Hafkamp Florianne
- Hagens Laura
- Hagin David
- Haguenauer Didier
- Halwani Rabih
- Hamann Jorg
- Hammal Soumeya
- Hammarström Lennart
- Hammoudi Nadjib
- Hancerli Selda
- Hanitsch Leif Gunnar
- Hanon Olivier
- Hariyan Tetyana
- Harris Vanessa
- Harrois Anarole
- Hatipoglu Nevin
- Hatipoğlu Nevin
- Hausfater Pierre
- Hautem Coraline
- Heath James R.
- Heijmans Catherine
- Hekimian Guillaume
- Heming Nicholas
- Hemke Robert
- Hendou Samia
- Henrickson Sarah E.
- Heppekcan Deniz
- Hermine Olivier
- Hernandez-Brito Elisa
- Heunks Sabine M. Hermans Leo
- Ho Po-ki
- Ho Sylvie
- Hoctin Alexandre
- Hoffmann Isabelle
- Holanda-Peña María Soledad
- Hollmann Markus
- Horcajada Juan P.
- Horn Janneke
- Hoste Eric
- Hoste Levi
- Houas Ikram
- Houhou Nadhira
- Houllier Marie
- Hovius Joppe W.
- Hraiech Sami
- Hsieh Elena W. Y.
- Hulot Jean-Sébastien
- Humbert Linda
- Hung Ivan F. N.
- Huot Benjamin
- Hupalo Daniel N.
- Huscenot Tessa
- Husebye Eystein
- Iglesias Alejandro D.
- Ikherbane Ghilas
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- Imarazene Meriem
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- Mathian Alexis
- Matos Larissa R. B.
- Matthews Gail V.
- Mattiaccio Alessandro
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- Mayaux Julien
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- Messani Fadhila
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- Million Matthieu
- Milner Joshua D.
- Minka Fadi Hillary
- Mirault Tristan
- Mircher Clotilde
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- Mirsaeidi Mehdi
- Miyara Makoto
- Mizoguchi Yoko
- Modi Bhavi P.
- Mogensen Trine H.
- Moine Pierre
- Mojoli Francesco
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- Morbieu Caroline
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- Mortelette Helene
- Mouly Stéphane
- Mouly Stéphane J.
- Mouquet Hugo
- Mullaert Jimmy
- Muzaffar Rosita
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- Mège Jean-Louis
- Nacerddine Cherifa Iness
- Nadal Marine
- Nadif Hajer
- Nadji Seyed Alireza
- Naesens Leslie
- Nafati Cyril
- Nagashima Shintaro
- Nakagama Yu
- Narvaez Rafael Usubillaga
- Nassarmadji Kladoum
- Natella Pierre
- Ndingamondze Sandrine
- Neant Nadège
- Nellen Jeaninne
- Neraal Stefan
- Neven Bénédicte
- Neves João Farela
- Ng Lisa F. P.
- Ng Lisa F. P.
- Ng Yuk-Yung
- Nguyen Caroline
- Nguyen Duc
- Nguyen Duc
- NIAID-USUHS COVID Study Group [missing]
- Nicolas Leturque
- Nielly hubert
- Nlomenyengue Luc
- Noel Nicolas
- Noret Marion
- Nossent Esther J.
- Notarangelo Luigi D.
- Notarangelo Luigi D.
- Nouroudine Mariama
- Novelli Antonio
- Novelli Giuseppe
- Nseir Saad
- Nunes Hilario
- Nussbaum Robert
- N’Guyen Bao
- Ocejo-Vinyals J. Gonzalo
- Okada Satoshi
- Okamoto Keisuke
- Oler Andrew J.
- Omar Edris
- Orchestra Working Group [missing]
- Oualha Mehdi
- Ouazene Zineb
- Ouedrani Amani
- Ouedraogo Elise
- Ouelaa Wassila
- Oufella Hafid Ait
- Oukhedouma Anissa
- Oya Herve
- Ozcelik Tayfun
- Oziel Johanna
- Ozkaya-Parlakay Aslinur
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- Padilla Thomas
- Pagani Michele
- Paillaud Elena
- Paiva Solenne
- Palabiyik Figen
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- Papadopoulos Aurélie
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- Paris Christophe
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- Parizot Christophe
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- Paul Christelle
- Paul Stéphane
- Paulus Frederique
- Pavot Arthur
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- Pham Huong
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- Pietri Olivia
- Pina-Fuentes Dan A. I.
- Pinson Michelle
- Pintado Claire
- Pippucci Tommaso
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- Piquard Valentine
- Piquard Valentine
- Piralla Antonio
- Pires Christine
- Pistone Thierry
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- Planas-Serra Laura
- Planquette Benjamin
- Pleguezuelo Daniel E.
- Ploin Dominique
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- Poissy Julien
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- Poncelet Géraldine
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- Ponscarme Diane
- Poulakou Garyphallia
- Pouletty Marie S.
- Pourcelot Annegaelle
- Pourcher Valérie
- Pourshahnazari Persia
- Pouvaret Anne
- Prando Carolina
- Preckel Bennedikt
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- Previlon Miresta
- Prevost Margot
- Prins Jan M.
- Provoost Marie-Julie
- Puel Anne
- Pueyo David Martínez
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- Pérez-Fernández Xosé Luis
- Qiu-Chen Jia Li
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- Raphalen Jean Herle
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- Richard Mariecaroline
- Rigo-Bonnin Raúl
- rivet Nadia
- Rivière Jacques G.
- Robert Maxence
- Rocamora-Blanch Gemma
- Rodero Mathieu P.
- Rodrigo Carlos
- Rodriguez Luis Antonio
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- Rodriguez-Palmero Agustí
- Rodríguez-Gallego Carlos
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- Schrauwen Femke A. P.
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- Schultz Marcus J.
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- Seppänen Mikko R. J.
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- Skandri Lina Innes
- Slabbynck Hans
- Slaby Ondrej
- Slim Marleen A.
- Slimani Miassa
- Smadja David M.
- Smeele Patrick
- Smit Marry
- Smith Nikaia
- Snauwaert Aurélie
- Snow Andrew L.
- Snow Andrew L.
- Sobh Ali
- Sokol Harry
- Solanich Xavier
- Soler Catherine
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- Soyer Benjamin
- Sozeri Betul
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- Steg Gabriel
- Stella Giulia Maria
- Stepanovskiy Yuriy
- Stijnis Cornelis S.
- Stilma Willemke
- Stoclin Annabelle
- Su Helen C.
- Su Helen C.
- Su Richa
- Suarez Lydia
- Sukumar Gauthaman
- Szwebel Tali-Anne
- Sánchez-Montalvá Adrián
- Sánchez-Ramón Silvia
- Sözeri Betül
- Taccone Fabio
- Tacconelli Evelina
- Taffame Kossi
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- Tancevski Ivan
- Tandjaoui-Lambiotte Yacine
- Tangye Stuart G.
- Tantet Claire
- Tardivon Coralie
- Tardy Bernard
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- Taupin Jean-Luc
- Tavernier Simon
- Tellier Marie-Capucine
- Tello Loreto Vidaur
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- Thiebaud Pierre clement
- Thiery Guillaume
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- Thoral Patrick
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- Thumerelle Caroline
- Thy Michael
- Tiercelet Kelly
- Timsit Jean-François
- Tipu Imran
- Tisserand Julie
- Tolstrup Martin
- Tomasoni Gabriele
- Tomczak Carole
- Tompkins Miranda F.
- Torelino Krystel
- Touam-Ext Fatima
- Toubiana Julie
- Toumi Lilia
- Toury Gustave
- Toy-Miou Mireille
- Trandinh Alexy
- Treluyer Jean-Marc
- Tresoldi Cristina
- Triantafyllia Vasiliki
- Trinque Baptiste
- Trouillet-Assant Sophie
- Troya Jesus
- Troya Jesús
- Truchot Jennifer
- Tsang Owen T. Y.
- Tserel Liina
- Tso Eugene Y. K.
- Tsonas Anissa M.
- Tual Christelle
- Tubach Florence
- Tubiana Sarah
- Tucci Alessandra
- Tuinman Pieter R.
- Tunesi Simone
- Turpin Agathe
- Turpin Matthieu
- Turvey Stuart E.
- Téoulé François
- Uddin Furkan
- Uddin Mohammed J.
- Urbina Tomas
- Ursini Matilde Valeria
- Utsumi Takanori
- Uzunhan Yurdagul
- Uzunhan Yurdagul
- Vabres Pierre
- Vacher Yannick
- Vaittinadaayar Prabakar
- Valencia-Ramos Juan
- Valent Arnaud
- Valentian Maelle
- Valin Nadia
- Vallet Hélène
- Valsecchi Maria Grazia
- van Agtmael Michiel
- van Baarle Frank
- Van Braeckel Eva
- van de Beek Diederik
- van de Beek Diederik
- van de Beek Diederik
- Van Den Rym Ana Maria
- van der Poll Tom
- van der Valk Marc
- Van Der Werf Sylvie
- van der Werf Sylvie
- van Mourik Niels
- Van Praet Jens
- van Vugt Michèle
- Vanderlinden Dimitri
- Vandernoot Isabelle
- Vanel Noémie
- Vaz Marina
- Vazquezibarra Miguel-Alejandro
- Vedie Benoit
- Veelo Denise
- Vega Clara Campos
- Veislinger Aurélie
- Velez-Santamaria Valentina
- Veliz Silvia Patricia Zuniga
- Velly Laetitia
- Verstuyft Celine
- Viallette Cedric
- Vicaut Eric
- Vidaud Michel
- Vidigal Mateus C.
- Viel Sébastien
- Vignali Valérie
- Vignes Dorothee
- Vilaire-Meunier Marie E.
- Villain Cédric
- Villar-García Judit
- Vimpere Damien
- Vincent Audrey
- Vinh Donald C.
- Virlouvet Myriam
- Visseaux Benoit
- Visseaux Benoit
- Vlaar Alexander P. J.
- Voiriot Guillaume
- Voiriot Guillaume
- Voisot Lena
- Volleman Carolien
- Volokha Alla
- von Bernuth Horst
- Vught Lonneke A.
- Vuotto Fanny
- Waucquier Nawal
- Wauters Els
- Wauters Joost
- Weiss Emmanuel
- Weiss Nicolas
- Wiedemann Aurélie
- Wiersinga W. Joost
- Wilkerson Matthew D.
- Winchenne Anaïs
- Wouters Dorien
- Wu Alan K. L.
- Wu Tak-Chiu
- Yahşi Aysun
- Yasar Kadriye Kart
- Yazdanpanah Yazdan
- Yazdanpanah Yazdan
- Yesilbas Osman
- Yildiz Mehmet
- Yordanov Youri
- Youkou Christy Gaëlla Kotokpo
- Young Barnaby E.
- Yüksek Saliha Kanık
- Yükselmiş Ufuk
- Zafrani Lara
- Zaidan Mohamad
- Zaidi Wissem
- Zak Cathia
- Zarhrate-Ghoul Aida
- Zatout Ouassila
- Zatz Mayana
- Zatz Mayana
- Zatz Mayana
- Zawadzki Pawel
- Zecca Marco
- Zeino Suzanne
- Zeitouni Michel
- Zemirli Naïma
- Zerah Lorene
- Zhang Peng
- Zhang Qian
- Zhang Shen-Ying
- Zhang Xijun
- Zhang Yu
- Zia Ounsa
- Ziol Marianne
- Zolario Oceane
- Zuber Julien
- Zuccaro Valentina
- Zwinderman A. H.
- Íñigo-Campos Antonio
- Öz Şadiye Kübra Tüter
- Özkan Esra Akyüz
- Özçelik Tayfun
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 01/01/2023
- Field of study
BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old